Flexile disposable bioreactors are fast becoming the most desirable means of manufacturing biological products. However, the application of these devices has been severely restricted because of the inability to provide high aeration and exhaust needed to grow bacteria and other organisms and cells and as a result, the applications of the two dimensional flexible bioreactors has remained restricted to cell culture that does not need high degree of gasification. Even when disposable flexible bioreactors are used for cell culture, their sizes have been limited again by the quantity of gas that can be provided inside the bioreactor and more important how fast the gas can be removed from the bioreactors.
The reason why the two dimensional flexible bag technology has not found its deserved place in the manufacturing systems is that much of the thinking that went into a creating three-dimensional technology was carried over to the two-dimensional world. A one less dimension meant a one giant change in thinking that never came. There is a need to take a fresh look at the core technology and revamp it to make the flexible bag more useful in the manufacturing of biological drugs. In the words of one of the most famous poets of Asia, Mirza Asadullah Khan Ghalib as translated by the inventor:
A monotheist we are, it is in our resolve to reject traditions. When dogmas are decimated, they become ingredients of a new belief.”
Growing bacteria requires extensive aeration and thus very large exhaust outlets and while this would not be an issue for the hard-walled bioreactors. Flexible bioreactors have the problem of changes in the pressure as bags expand and contract carrying the risk of drawing room air inside the bag and also of exhausting liquid particles carrying biological culture that will contaminate the room. There is also the problem of any liquid particles laden with live organisms leaving the bioreactor to the environment. To overcome these problems, the exhaust port of disposable bioreactors in the current art is provided with a filter that prevents both incidences. This works well as long as the volume of gas exhausted is small but when hundreds of liters of air will be exhausted out, this will require extremely large filters and even then, building a backpressure will be inevitable.
It is important to know that while cell culture growth in the flexible bags is promoted by exchange of gases across the surface while the bags build a certain pressure, growth of bacterial cultures requires intense aeration that can not be accomplished by surface aeration and thus pressurization is useless and can even be damaging to the bioreactor as large volumes are passed through the bag and even small changes in the resistance to flow would add significant pressurization of the flexible bags.
Large exhausting of gases also carries the risk of loosing moisture from the bags resulting in significant volume changes.
There is no prior art in the field of bioreactor exhaust systems suitable for disposable flexible bags when used to grow bacteria or other cells and organisms require large volume of exhausts.